<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Xianfang Wu</style></author><author><style face="normal" font="default" size="100%">Viet Loan Dao Thi</style></author><author><style face="normal" font="default" size="100%">Liu, Peng</style></author><author><style face="normal" font="default" size="100%">Constantin N Takacs</style></author><author><style face="normal" font="default" size="100%">Kuanhui Xiang</style></author><author><style face="normal" font="default" size="100%">Linda Andrus</style></author><author><style face="normal" font="default" size="100%">Jérôme Gouttenoire</style></author><author><style face="normal" font="default" size="100%">Darius Moradpour</style></author><author><style face="normal" font="default" size="100%">Charles M. Rice</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Pan-Genotype Hepatitis E Virus Replication in Stem Cell-Derived Hepatocellular Systems</style></title><secondary-title><style face="normal" font="default" size="100%">Gastroenterology </style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://pubmed.ncbi.nlm.nih.gov/29277559/</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">154</style></volume><pages><style face="normal" font="default" size="100%">663-674</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">
&lt;strong class=&quot;sub-title&quot;&gt;Background &amp;amp; aims:&amp;nbsp;&lt;/strong&gt;The 4 genotypes of hepatitis E virus (HEV) that infect humans (genotypes 1-4) vary in geographical distribution, transmission, and pathogenesis. Little is known about the properties of HEV or its hosts that contribute to these variations. Primary isolates grow poorly in cell culture; most studies have relied on variants adapted to cancer cell lines, which likely alter virus biology. We investigated the infection and replication of primary isolates of HEV in hepatocyte-like cells (HLCs) derived from human embryonic and induced pluripotent stem cells.
&lt;strong class=&quot;sub-title&quot;&gt;Methods:&amp;nbsp;&lt;/strong&gt;Using a cell culture-adapted genotype 3 strain and primary isolates of genotypes 1 to 4, we compared viral replication kinetics, sensitivity to drugs, and ability of HEV to activate the innate immune response. We studied HLCs using quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence assay and enzyme-linked immunosorbent assays. We used an embryonic stem cell line that can be induced to express the CRISPR-Cas9 machinery to disrupt the peptidylprolyl isomerase A gene, encoding cyclophilin A (CYPA), a protein reported to inhibit replication of cell culture-adapted HEV. We further modified this line to rescue expression of CYPA before terminal differentiation to HLCs and performed HEV infection studies.
&lt;strong class=&quot;sub-title&quot;&gt;Results:&amp;nbsp;&lt;/strong&gt;HLCs were permissive for infection by nonadapted, primary isolates of HEV genotypes 1 to 4. HEV infection of HLCs induced a replication-dependent type III interferon response. Replication of primary HEV isolates, unlike the cell culture-adapted strain, was not affected by disruption of the peptidylprolyl isomerase A gene or exposure to the CYPA inhibitor cyclosporine A.
&lt;strong class=&quot;sub-title&quot;&gt;Conclusions:&amp;nbsp;&lt;/strong&gt;Cell culture adaptations alter the replicative capacities of HEV. HLCs offer an improved, physiologically relevant, and genetically tractable system for studying the replication of primary HEV isolates. HLCs could provide a model to aid development of HEV drugs and a system to guide personalized regimens, especially for patients with chronic hepatitis E who have developed resistance to ribavirin.

&lt;strong class=&quot;sub-title&quot;&gt;Keywords:&amp;nbsp;&lt;/strong&gt;Antiviral; HLCs; Personalized Medicine; Primary Isolates.</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue></record></records></xml>